CRYSTAL STRUCTURES OF SIGMA 54-INTERACTING TRANSCRIPTION FACTORS

Stanford University, Stanford CA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We are studying prokaryotic transcription factors that interact with RNA polymerase holoenzyme containing the alternate sigma factor, sigma 54. Three domains comprise these ?NtrC-like? transcription factors: the N-terminal regulatory domain, the central ATPase domain, and the DNA-binding domain. Foundational structures solved in our lab were the NtrC regulatory domain and a solution structure of the NtrC DNA-binding domain. These single-domain structures provided key insight to the regulatory mechanisms of activation and oligomerization, but many fundamental questions remained: how do the three domains interact during different states of activation, i.e. how is signal propagated? What residues are important at the active sites and how do they perform their specific functions? What is the role of DNA binding and how does it change during the stages of activation? We recently obtained several structures from one NtrC ortholog from the extreme thermophile, Aquifex aeolicus, and are now pursuing other structures of NtrC-like activators found in A. aeolicus. New structures will allow us to assign structure-function relationships to better understand this family as a whole, and to generate basic knowledge relevant to all transcription factors.